Evidence map›Paper›PMID 22936357›Full record

ArticleAmerican journal of respiratory and critical care medicine2012

Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation.

Adam J Booth, Ryan Hadley, Ashley M Cornett, Alyssa A Dreffs, Stephanie A Matthes, Jessica L Tsui, Kevin Weiss, Jeffrey C Horowitz, Vincent F Fiore, Thomas H Barker and 4 more

Open access · greenAbstract read
In one paragraph

Article in American journal of respiratory and critical care medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 392 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
392citing papers in PubMed, 1 pooled it
32.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

392 citing papers in PubMed, 1 synthesis or guideline pooled it, 673 citations in OpenAlex.

  1. [Biomechanical properties of epithelial mesenchymal transition in idiopathic pulmonary fibrosis].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2023
    Pooled it
  2. Bexotegrast Shows Dose-Dependent Integrin αAnnals of the American Thoracic Society · 2025
    Trial
  3. Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis: The INTEGRIS-IPF Clinical Trial.American journal of respiratory and critical care medicine · 2024
    Trial
  4. A practical toolbox for modelling fibrosis in vitro.Nature biomedical engineering · 2026
    Review
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  17. Microengineered Gradient Hydrogels for Mechanobiology.Advanced healthcare materials · 2026
    Review
  18. Review
  19. Article
  20. Article

332 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Adam J BoothDivision of Pulmonary and Critical Care Medicine, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5642, USA.
Ryan Hadley
Ashley M Cornett
Alyssa A Dreffs
Stephanie A Matthes
Jessica L Tsui
Kevin Weiss
Jeffrey C Horowitz
Vincent F Fiore
Thomas H Barker
Bethany B Moore
Fernando J Martinez
Laura E Niklason
Eric S White
University of Michigan · USGeorgia Institute of Technology · USYale University · US

Funding

PULMONARY CELLULAR AND MOLECULAR BIOLOGY TRAININGT32HL007749 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Robert Pickett Dickson · 1993 to 2026
$19.9M
Matrix and Bioreactors for Human Lung RegenerationU01HL111016 · NHLBI · YALE UNIVERSITY · PI NIKLASON, LAURA E, WHITE, ERIC S · 2012 to 2016
$3.2M
Lung Tissue EngineeringR01HL098220 · NHLBI · YALE UNIVERSITY · PI NIKLASON, LAURA E · 2010 to 2013
$2.5M
Mesenchymal Cell Fate Determination by Extracellular Matrix StiffnessR01HL105489 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HOROWITZ, JEFFREY C · 2011 to 2015
$1.9M
Role of EIIIA fibronectin in pulmonary fibrosisR01HL085083 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WHITE, ERIC S · 2007 to 2011
$1.9M
NHLBI NIH HHS R01 HL085083NHLBI NIH HHS R01 HL098220NHLBI NIH HHS R01 HL105489NHLBI NIH HHS T32 HL007749NHLBI NIH HHS T32 HL07749NHLBI NIH HHS U01 HL111016
6 · The paper itself

Abstract

rationaleExtracellular matrix (ECM) is a dynamic tissue that contributes to organ integrity and function, and its regulation of cell phenotype is a major aspect of cell biology. However, standard in vitro culture approaches are of unclear physiologic relevance because they do not mimic the compositional, architectural, or distensible nature of a living organ. In the lung, fibroblasts exist in ECM-rich interstitial spaces and are key effectors of lung fibrogenesis.

objectivesTo better address how ECM influences fibroblast phenotype in a disease-specific manner, we developed a culture system using acellular human normal and fibrotic lungs.

methodsDecellularization was achieved using treatment with detergents, salts, and DNase. The resultant matrices can be sectioned as uniform slices within which cells were cultured. MEASUREMENTS AND MAIN

resultsWe report that the decellularization process effectively removes cellular and nuclear material while retaining native dimensionality and stiffness of lung tissue. We demonstrate that lung fibroblasts reseeded into acellular lung matrices can be subsequently assayed using conventional protocols; in this manner we show that fibrotic matrices clearly promote transforming growth factor-β-independent myofibroblast differentiation compared with normal matrices. Furthermore, comprehensive analysis of acellular matrix ECM details significant compositional differences between normal and fibrotic lungs, paving the way for further study of novel hypotheses.

conclusionsThis methodology is expected to allow investigation of important ECM-based hypotheses in human tissues and permits future scientific exploration in an organ- and disease-specific manner.

Indexed as

Blotting, WesternExtracellular MatrixFibroblastsHumansLungMass SpectrometryMicroscopy, ElectronPulmonary FibrosisSpectrophotometry, AtomicTissue Culture Techniques

Identifiers

PMID22936357
PMCPMC3530219
OpenAlexW2062461864

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.